title: Pathology of non-thermal irreversible electroporation (N-TIRE)-induced ablation of the canine brain.
abstract: This study describes the neuropathologic features of normal canine brain ablated with non-thermal irreversible electroporation (N-TIRE). The parietal cerebral cortices of four dogs were treated with N-TIRE using a dose-escalation protocol with an additional dog receiving sham treatment. Animals were allowed to recover following N-TIRE ablation and the effects of treatment were monitored with clinical and magnetic resonance imaging examinations. Brains were subjected to histopathologic and ultrastructural assessment along with Bcl-2, caspase-3, and caspase-9 immunohistochemical staining following sacrifice 72 h post-treatment. Adverse clinical effects of N-TIRE were only observed in the dog treated at the upper energy tier. MRI and neuropathologic examinations indicated that N-TIRE ablation resulted in focal regions of severe cytoarchitectural and blood-brain-barrier disruption. Lesion size correlated to the intensity of the applied electrical field. N-TIRE-induced lesions were characterized by parenchymal necrosis and hemorrhage; however, large blood vessels were preserved. A transition zone containing parenchymal edema, perivascular inflammatory cuffs, and reactive gliosis was interspersed between the necrotic focus and normal neuropil. Apoptotic labeling indices were not different between the N-TIRE-treated and control brains. This study identified N-TIRE pulse parameters that can be used to safely create circumscribed foci of brain necrosis while selectively preserving major vascular structures.
authors.affiliation: Department of Small Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA. jrossmei@vt.edu.
authors.forename: John H
authors.initials: JH
authors.lastname: Rossmeisl
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Garcia
authors.forename: John L
authors.initials: JL
authors.lastname: Roberston
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Ellis
authors.forename: Rafael V
authors.initials: RV
authors.lastname: Davalos
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000601:surgery / Q000648:ultrastructure; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D004285:Dogs; D018274:Electroporation / Q000662:veterinary; D008279:Magnetic Resonance Imaging / Q000379:methods; D046529:Microscopy, Electron, Transmission; D009336:Necrosis / Q000378:metabolism / Q000473:pathology; D019635:Neurosurgical Procedures / Q000009:adverse effects*
chemical_list: D053148:Caspase 3; D053453:Caspase 9
keywords: central nervous system; dog; irreversible electroporation; neuropathology